Catrina Sims, Lucy Seay, Subhrajit Bhattacharya, Vishnu Suppiramaniam

Abstract

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) subtype of glutamate receptors mediates fast excitatory neurotransmission in the mammalian central nervous system and are implicated in memory impairment associated with several neurodegenerative disorders.  Carefully controlled modulation of AMPA receptors is critical for normal synaptic transmission. Several endogenous molecules play a vital role in regulating the functional properties of AMPA receptors.  Polysialic acid (PSA), a highly negatively charged, carbohydrate, covalently attached to the neural cell adhesion molecule (NCAM), is highly expressed in hippocampal synapses and alters the single channel properties of AMPA receptors.  However, the effects of PSA on native synaptic AMPA receptors have never been investigated. This study utilized biochemical isolation and functional reconstitution of synaptosomal AMPA receptors in lipid bilayers to elucidate the effects of PSA on synaptic AMPA receptors.  PSA, in a concentration dependent manner, increases the single channel open probability and mean open time, and decreases the mean closed time. The results indicate that PSA potently modulates synaptic AMPA receptors. Modulation of AMPA receptors is a possible strategy to ameliorate memory deficits in neurodegenerative conditions. Therefore, molecules derived from PSA could be a potential therapeutic option to treat memory loss in neurodegenerative diseases.

Catrina Sims

Email: robinsoc@musc.edu